An Update on Clinical Trials and Potential Therapeutic Strategies in T-Cell Acute Lymphoblastic Leukemia.

An Update on Clinical Trials and Potential Therapeutic Strategies in T-Cell Acute Lymphoblastic Leukemia.
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DOI:
10.3390/ijms24087201
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发表时间:
2023-04-13
影响因子:
5.6
通讯作者:
Wang, Haizhen
Wang, Haizhen
中科院分区:
生物学2区
文献类型:
--
作者:
Patel, Janisha;Gao, Xueliang;Wang, Haizhen

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目前T细胞急性白血病的治疗是基于风险分层,并大大提高了患者的生存率,但由于疾病复发,治疗耐药性或治疗相关的毒性/感染,死亡率仍然很高。复发性疾病患者的预后仍然很差。在过去的几年里,已经研究了新的药物,以优化高危患者的前期治疗,希望降低复发率。本文综述了奈拉滨/硼替佐米/CDK 4/6抑制剂治疗T-ALL的临床研究进展,以及针对NOTCH诱导的T-ALL的新策略。我们还概述了使用单克隆/双特异性T细胞接合抗体、抗PD 1/抗PDL 1检查点抑制剂和CAR-T进行T-ALL治疗的免疫治疗临床试验。总体而言,临床前研究和临床试验表明,将单克隆抗体或CAR-T应用于复发/难治性T-ALL治疗是有希望的。靶向治疗与免疫治疗的结合可能成为T-ALL治疗的新策略。
Current therapies for T-cell acute leukemia are based on risk stratification and have greatly improved the survival rate for patients, but mortality rates remain high owing to relapsed disease, therapy resistance, or treatment-related toxicities/infection. Patients with relapsed disease continue to have poor outcomes. In the past few years, newer agents have been investigated to optimize upfront therapies for higher-risk patients in the hopes of decreasing relapse rates. This review summarizes the progress of chemo/targeted therapies using Nelarabine/Bortezomib/CDK4/6 inhibitors for T-ALL in clinical trials and novel strategies to target NOTCH-induced T-ALL. We also outline immunotherapy clinical trials using monoclonal/bispecific T-cell engaging antibodies, anti-PD1/anti-PDL1 checkpoint inhibitors, and CAR-T for T-ALL therapy. Overall, pre-clinical studies and clinical trials showed that applying monoclonal antibodies or CAR-T for relapsed/refractory T-ALL therapy is promising. The combination of target therapy and immunotherapy may be a novel strategy for T-ALL treatment.
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